Trial Outcomes & Findings for Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients (NCT NCT02152345)
NCT ID: NCT02152345
Last Updated: 2021-02-10
Results Overview
To assess whether treatment with Thymoglobulin induction and belatacept based maintenance immunosuppression would reduce delayed graft function (DGF) rates among recipients of deceased donor renal transplants as measured by clinical findings and NGAL marker, as specified below and defined by others. This will be compared to the incidence of DGF in patients treated with a Tacrolimus based regimen. Patients who require hemodialysis in the first 7 days after transplantation and/or patients whose serum creatinine decreases \<10% during 3 consecutive days after the transplant will be considered to have DGF in the absence of other confounding factors such as obstruction or infection. NGAL will be used as a verification marker of DGF.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
57 participants
Primary outcome timeframe
Up to 3 months post-transplantation
Results posted on
2021-02-10
Participant Flow
Patients called into the hospital for potential renal transplants were approached for possible participation in the study if they agreed to discuss research and were eligible per study criteria. Patients were given the option to participate or decline.
Participant milestones
| Measure |
Belatacept Immunosuppression
Renal transplant recipients will receive Methylprednisolone, rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Belatacept 10 mg/kg will be administered in the operating room \~1 hr prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: 5, 14, 30, 56, \& 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Standard of Care:
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered Day 0-3.
|
Standard Immunosuppression (Tacrolimus)
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Tacrolimus 0.05 mg/kg PO every 12 hrs will be on Day 0 after transplantation. It will then be administered on the following post-transplantation days: 3-90 at 8-12ng/mL; Day 91-180 at 8-10 ng/mL.
Standard of Care:
* Tacrolimus 6 - 8 ng/mL administered daily thereafter until end of study.
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
|
|---|---|---|
|
Overall Study
STARTED
|
28
|
29
|
|
Overall Study
COMPLETED
|
24
|
24
|
|
Overall Study
NOT COMPLETED
|
4
|
5
|
Reasons for withdrawal
| Measure |
Belatacept Immunosuppression
Renal transplant recipients will receive Methylprednisolone, rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Belatacept 10 mg/kg will be administered in the operating room \~1 hr prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: 5, 14, 30, 56, \& 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Standard of Care:
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered Day 0-3.
|
Standard Immunosuppression (Tacrolimus)
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Tacrolimus 0.05 mg/kg PO every 12 hrs will be on Day 0 after transplantation. It will then be administered on the following post-transplantation days: 3-90 at 8-12ng/mL; Day 91-180 at 8-10 ng/mL.
Standard of Care:
* Tacrolimus 6 - 8 ng/mL administered daily thereafter until end of study.
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
|
|---|---|---|
|
Overall Study
Case Cancellations
|
2
|
4
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
Baseline Characteristics
Belatacept Compared to Tacrolimus in Deceased Donor Renal Transplant Recipients
Baseline characteristics by cohort
| Measure |
Belatacept Immunosuppression
n=28 Participants
Renal transplant recipients will receive Methylprednisolone, rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Belatacept 10 mg/kg will be administered in the operating room \~1 hr prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: 5, 14, 30, 56, \& 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Standard of Care:
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered Day 0-3.
|
Standard Immunosuppression (Tacrolimus)
n=29 Participants
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Tacrolimus 0.05 mg/kg PO every 12 hrs will be on Day 0 after transplantation. It will then be administered on the following post-transplantation days: 3-90 at 8-12ng/mL; Day 91-180 at 8-10 ng/mL.
Standard of Care:
* Tacrolimus 6 - 8 ng/mL administered daily thereafter until end of study.
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
|
Total
n=57 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
21 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
46 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Age, Continuous
|
57.4 years
n=99 Participants
|
53.8 years
n=107 Participants
|
55.6 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
39 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Up to 3 months post-transplantationTo assess whether treatment with Thymoglobulin induction and belatacept based maintenance immunosuppression would reduce delayed graft function (DGF) rates among recipients of deceased donor renal transplants as measured by clinical findings and NGAL marker, as specified below and defined by others. This will be compared to the incidence of DGF in patients treated with a Tacrolimus based regimen. Patients who require hemodialysis in the first 7 days after transplantation and/or patients whose serum creatinine decreases \<10% during 3 consecutive days after the transplant will be considered to have DGF in the absence of other confounding factors such as obstruction or infection. NGAL will be used as a verification marker of DGF.
Outcome measures
| Measure |
Belatacept Immunosuppression
n=24 Participants
Renal transplant recipients will receive Methylprednisolone, rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Belatacept 10 mg/kg will be administered in the operating room \~1 hr prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: 5, 14, 30, 56, \& 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Standard of Care:
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered Day 0-3.
|
Standard Immunosuppression (Tacrolimus)
n=24 Participants
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Tacrolimus 0.05 mg/kg PO every 12 hrs will be on Day 0 after transplantation. It will then be administered on the following post-transplantation days: 3-90 at 8-12ng/mL; Day 91-180 at 8-10 ng/mL.
Standard of Care:
* Tacrolimus 6 - 8 ng/mL administered daily thereafter until end of study.
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
|
|---|---|---|
|
Number of Participants With Delayed Graft Function (DGF)
|
12 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: Up to 1 year post-transplantationAllograft survival is defined as functioning renal transplant.
Outcome measures
| Measure |
Belatacept Immunosuppression
n=24 Participants
Renal transplant recipients will receive Methylprednisolone, rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Belatacept 10 mg/kg will be administered in the operating room \~1 hr prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: 5, 14, 30, 56, \& 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Standard of Care:
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered Day 0-3.
|
Standard Immunosuppression (Tacrolimus)
n=24 Participants
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Tacrolimus 0.05 mg/kg PO every 12 hrs will be on Day 0 after transplantation. It will then be administered on the following post-transplantation days: 3-90 at 8-12ng/mL; Day 91-180 at 8-10 ng/mL.
Standard of Care:
* Tacrolimus 6 - 8 ng/mL administered daily thereafter until end of study.
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
|
|---|---|---|
|
Percentage of Participants With Allograft Survival
|
24 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: Up to 1 year post-transplantationAll rejection episodes will be confirmed by renal transplant biopsy provoked by change in renal function not explained by other clinical causes.
Outcome measures
| Measure |
Belatacept Immunosuppression
n=24 Participants
Renal transplant recipients will receive Methylprednisolone, rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Belatacept 10 mg/kg will be administered in the operating room \~1 hr prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: 5, 14, 30, 56, \& 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Standard of Care:
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered Day 0-3.
|
Standard Immunosuppression (Tacrolimus)
n=24 Participants
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Tacrolimus 0.05 mg/kg PO every 12 hrs will be on Day 0 after transplantation. It will then be administered on the following post-transplantation days: 3-90 at 8-12ng/mL; Day 91-180 at 8-10 ng/mL.
Standard of Care:
* Tacrolimus 6 - 8 ng/mL administered daily thereafter until end of study.
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
|
|---|---|---|
|
Number of Participants With an Allograft Rejection Episode
|
7 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Up to 1 year post-transplantationEstimated glomerular filtration rate (eGFR) is based on a blood sample (serum creatinine value), age, race, and gender. eGFR estimates best the function of the kidney at any one time.
Outcome measures
| Measure |
Belatacept Immunosuppression
n=24 Participants
Renal transplant recipients will receive Methylprednisolone, rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Belatacept 10 mg/kg will be administered in the operating room \~1 hr prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: 5, 14, 30, 56, \& 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Standard of Care:
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered Day 0-3.
|
Standard Immunosuppression (Tacrolimus)
n=24 Participants
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Tacrolimus 0.05 mg/kg PO every 12 hrs will be on Day 0 after transplantation. It will then be administered on the following post-transplantation days: 3-90 at 8-12ng/mL; Day 91-180 at 8-10 ng/mL.
Standard of Care:
* Tacrolimus 6 - 8 ng/mL administered daily thereafter until end of study.
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
|
|---|---|---|
|
Estimated Glomerular Filtration Rate (eGFR)
|
46 mL/min/1.73m^2
Standard Deviation 15.85
|
41 mL/min/1.73m^2
Standard Deviation 11.45
|
Adverse Events
Belatacept Immunosuppression
Serious events: 14 serious events
Other events: 5 other events
Deaths: 4 deaths
Standard Immunosuppression (Tacrolimus)
Serious events: 15 serious events
Other events: 3 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Belatacept Immunosuppression
n=24 participants at risk
Renal transplant recipients will receive Methylprednisolone, rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Belatacept 10 mg/kg will be administered in the operating room \~1 hr prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: 5, 14, 30, 56, \& 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Standard of Care:
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered Day 0-3.
|
Standard Immunosuppression (Tacrolimus)
n=24 participants at risk
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Tacrolimus 0.05 mg/kg PO every 12 hrs will be on Day 0 after transplantation. It will then be administered on the following post-transplantation days: 3-90 at 8-12ng/mL; Day 91-180 at 8-10 ng/mL.
Standard of Care:
* Tacrolimus 6 - 8 ng/mL administered daily thereafter until end of study.
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
|
|---|---|---|
|
Renal and urinary disorders
Delayed Graft Function
|
50.0%
12/24
|
62.5%
15/24
|
|
Renal and urinary disorders
Rejection
|
29.2%
7/24
|
45.8%
11/24
|
|
Infections and infestations
EBV quant+
|
12.5%
3/24
|
12.5%
3/24
|
|
Infections and infestations
CMV quant+
|
37.5%
9/24
|
20.8%
5/24
|
|
Infections and infestations
BK quant+
|
25.0%
6/24
|
12.5%
3/24
|
|
Renal and urinary disorders
Posttransplant lymphoproliferative disease
|
0.00%
0/24
|
4.2%
1/24
|
Other adverse events
| Measure |
Belatacept Immunosuppression
n=24 participants at risk
Renal transplant recipients will receive Methylprednisolone, rATG, Belatacept and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Belatacept 10 mg/kg will be administered in the operating room \~1 hr prior to kidney allograft reperfusion (Day 0). It will then be administered at 10 mg/kg on the following post-transplantation days: 5, 14, 30, 56, \& 84.
Belatacept 5 mg/kg will be administered every four weeks thereafter until end of study.
Standard of Care:
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered Day 0-3.
|
Standard Immunosuppression (Tacrolimus)
n=24 participants at risk
Renal transplant recipients will receive standard immunosuppressive therapy, including steroids (Methylprednisolone), rATG, Tacrolimus and Mycophenolate. Subjects will be followed for primary endpoint to Day 7 and Month 3 after transplantation and secondary endpoints of kidney function and patient and graft survival up to month 36 after transplantation.
Tacrolimus 0.05 mg/kg PO every 12 hrs will be on Day 0 after transplantation. It will then be administered on the following post-transplantation days: 3-90 at 8-12ng/mL; Day 91-180 at 8-10 ng/mL.
Standard of Care:
* Tacrolimus 6 - 8 ng/mL administered daily thereafter until end of study.
* Mycophenolate: 720 mg by mouth every 12 hours (Day 0)(1080 mg AA).
* rATG: 1.5 mg/kg IV daily on Day 0-3.
* Methylprednisolone: 500 mg (Day 0), 250mg (Day 1), 125mg (Day 2), 75 mg (Day 3) IV administered from Day 0-3.
|
|---|---|---|
|
Blood and lymphatic system disorders
Bleeding
|
20.8%
5/24
|
12.5%
3/24
|
|
Blood and lymphatic system disorders
Anemia
|
12.5%
3/24
|
8.3%
2/24
|
|
Renal and urinary disorders
Urinary Tract Infection
|
12.5%
3/24
|
4.2%
1/24
|
Additional Information
Dr. Mark A. Hardy
Columbia University Irving Medical Center
Phone: (212) 305-5502
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place